Research & Publications
Our laboratory is focused on the study of human immunodeficiency virus type I (HIV) replication and the development of small animal models of HIV. For example, mice are not susceptible to HIV due a profound block in HIV assembly and release from cells. We are exploring the nature of this block and are conducting genetic screens and biochemical assays to identify human genes that may be able to overcome this deficiency. Our work has zeroed in on host factor Crm1 and viral regulatory gene Rev; we have established a high throughput, cell-free assay in order to identify inhibitors of Rev function.
We also utilize replication-defective HIV as a vector to transduce non-dividing cells for gene therapeutic purposes and are developing novel methods of vector production. These vectors are used to investigate other viruses (for example, cellular binding and entry requirements of SARS-CoV-2, Ebola, and Western Equine Encephalitis) and to explore fundamental questions in molecular biology, such as high throughput identification of DNA elements that serve as transcriptional activators in various cell types, including human embryonic stem cells.
We are now funded through NIAID to use advanced molecular biology methods to identify both cis-acting DNA sequences and trans-acting protein factors that modulate CCR5 gene expression in primary human T cells and macrophages. CCR5 is a key co-receptor for many HIV isolates and eliminating CCR5 is central to the HIV cure effort. We have also been collaborating with investigators in Uganda to continue our studies of HIV+ elite controllers.
In collaboration with Dr. Priti Kumar, also of the ID section, we are funded by the NIH to examine the possibility of using adenoviral-vectored anti-HIV broadly neutralizing antibodies to counteract HIV, both as prophylaxis and as therapy, exploring their use in humanized murine models. In a somewhat related project we have constructed specialized adenovirus vectors in order to knock out the CCR5 gene in human progenitor cells, in vitro and in vivo.
Most recently, we have pivoted to COVID-19, and have been developing novel assays that quantify the functionality of the humoral immune response, after both natural infection and immunization. We recently published the development of a novel cell fusion assay to quantify the interaction between SARS-CoV-2 spike and hACE2, and we have a large, ongoing study to examine the humoral immune response after SARS-CoV-2 vaccination in US veterans.
Specialized Terms: HIV replication and the development of small animal models of HIV; HIV vectors; HIV replication and gene transfer into non-dividing cells, COVID-19, SARS-CoV-2.
HIV; Molecular Biology; SARS Virus; Infectious Disease Medicine
Public Health Interests